The proposed research is designed to extend our studies of cerebral asymmetry and depression. In previous research, we established that electrophysiological measures of anterior activation asymmetry are stable over time and appear to be associated with individual differences in affective reactivity and dispositional positive and negative affect. In addition, we found that depressed and non-depressed subjects differ in both resting and task-related asymmetries and that remitted depressives show resting asymmetries which are similar to depressives in an acute episode. In Experiment 1, we will assess the baseline and cognitive task-dependent asymmetry differences among endogenous depressives, non-endogenous depressives and controls. All subjects will be studied longitudinally and changes in clinical status will be tracked every two weeks. In addition, measures of baseline electrophysiology will be obtained at the same intervals. This design will permit us to examine relations between changes in clinical status and regional brain activity over time, both within and across subjects. Moreover, we will be able to specify whether changes in electrophysiological indices precede, accompany or succeed changes in clinical status. In this experiment, a series of cognitive tasks will also be presented during both the acute episode and upon recovery. Changes in cognitive performance and electrophysiology during the cognitive tasks will be examined between the acute episode and following recovery. In Experiment 2, endogenous depressives and controls will be assessed simultaneously on baseline electrophysiological measures and on measures of regional glucose metabolism with positron emission tomography (PET). Patients will be tested during an acute episode and following recovery. Controls will be tested at time intervals matched to the depressives. This will enable us to examine relations between measures of frontal activation asymmetry based upon the EEG and PET and to determine which features of each are state-dependent and state-independent. New procedures for precise anatomical localization using Magnetic Resonance Imaging will be utilized in this study. These studies will further our understanding of the neural mechanisms involved in depression and will provide critical new information on the use of measures of frontal activation asymmetry as state-independent markers of depression.